1. Amit Gupta, MS Swapnil M. Parchand, MBBS Jagat Ram, MS Arunaloke Chakrabarti, MD Amod Gupta, MS Advanced Eye Centre, Post Graduate Institute of Medical Education and Research Chandigarh, India. (eyepgi@sify.com) Authors have no financial interest in the subject matter of this poster. World Cornea Congress VI

2. Fungal keratitis  the second most common cause of blindness in developing countries. (Upadhyay et al, Am J Ophthalmol 1991; 111: 92-7) Relative incidence from India - >20% of post cataract surgery endophthalmitis -44% of all central corneal ulcers. (Gupta et al, Indian J Ophthalmol 2003;51:139-45) Risk factors for poor treatment outcome - -Natamycin monotherapy -large ulcer size -Aspergillus infection. (Prajna et al, Ophthalmol 2006; 113: 526-30) Fungal keratitis refractory to standard antifungal therapy - managed successfully on topical and oral voriconazole (case series). (Bunya et al, Am J Ophthalmol 2007; 143: 151-3) INTRODUCTION

3. Design: Prospective randomized interventional controlled study. Setting : Cornea services at tertiary care teaching hospital. Institute Ethics Committee clearance. Informed consent taken. 45 eyes of 45 patients with fungal corneal ulcer. Basic ophthalmological workup. To study the efficacy, outcomes and complications of oral and topical voriconazole in treatment of severe keratomycosis. Compare it with conventional antifungal treatment. AIM METHODS

4. Method Severe Fungal Corneal Ulcer 1.Infiltrates > 5 mm in longest diameter. 2.Infiltrates > 2/3 depth of corneal thickness. 3.Proven fungal corneal ulcer either on 10% KOH wet mount/Calcoflour white stain (CFW) or growth of fungi on Sabouraud’s dextrose agar (SDA). RANDOMISATION OF PATIENTS : Group I: Tab. Voriconazole 400 mg BD on Day 1 followed by 200 mg BD thereafter. Topical Voriconazole 1 % 1 hourly. Group II: Tab. Voriconazole 400 mg BD on Day 1 followed by 200 mg BD thereafter. Topical Natamycin 5 % suspension 1 hourly. Group III: Tab. Itraconazole 200 mg BD. Topical Natamycin 5 % suspension 1 hourly.

5. OUTCOME MEASURES : Treatment Failure: If the infiltrate and / or epithelial defect increase by 2 mm or more in size or increase in the size of hypopyon or endothelial plaque continued to enlarge for 3 consecutive days or perforation. Treatment success: Resolution of the corneal infiltrate with scarring, disappearance of the corneal endothelial plaque and hypopyon, and closure of the epithelial defect. Primary Outcome Measures: Time taken for resolution of epithelial defect, infiltrates and hypopyon. Secondary Outcome Measures: Anatomical outcome: - Corneal opacity at the end of 3 months. - Corneal vascularization at the end of 3 months. Funtional outcome: - Best corrected visual acuity at the end of 3 months.

6. Results : Ulcer Characteristics FactorsGroupnMean±Std deviationMinimumMaximum Infiltrate area (mm 2 )I15 38.3 ± 17.5 1370.4 II15 37.3 ± 11.2 24.868 III15 32.1 ± 12 1153.9 Total45 35.9 ± 13.9 1170.4 Epithelial defect area (mm 2 )I15 34.1 ± 14.4 18.168.8 II15 32.8 ± 12.5 21.472.2 III15 28.1 ± 11.9 1052.5 Total45 31.6 ± 12.9 1072.2 Hypopyon (mm)I11 1.7 ± 0.5 13 II14 1.6 ± 1.1 0.74 III12 1.9 ± 1.2 0.45 Total37 1.7 ± 1.24 0.45 The distribution of infiltrate area, epithelial defect area and size of hypopyon was not statistically significant between the three groups.

7. Results (Primary outcome) Factors Group nMean±Std deviation MaximumMinimumP value Time for resolution of infiltrates (days) I1036.8 ± 10.65520 II1138.8 ± 8.951280.860 III1036.7 ± 10.45217 Total3137.4 ± 9.75517 Time for resolution of epithelial defect (days) I1031.1 ± 11.45516 II1129.2 ± 8.245210.837 III1031.8 ± 11.45015 Total3130.6 ± 10.15515 Time for resolution of hypopyon (days) I69.8 ± 1.7127 II1012.3 ± 3.6186 III816 ± 10.541100.231 Total2412.9 ± 6.7416

8. Results Funtional outcome Group II Funtional outcome Group III

9. Surgical interventions InterventionIIIIIITotalP value No intervention9108270.712 ICAMB00110.343 AC wash+ICAMB01120.527 Conjunctiva flap11020.587 PK535130.667 ComplicationsGroup IGroup IIGroup IIITotalP value Cataract22150.775 Perforation545140.934 Glaucoma10120.553 Endophthalmitis01010.363 Pthisis bulbi01010.336 Complications (ICAMB- Intracameral Amphotericin B, PK- Penetrating keratoplasty)

10. Risk Factors For Poor Treatment Outcome N (%) Odds Ratio 95% C.I.P value LowerUpper Age (yrs)<45248.3451.15160.5000.036 >=4521 OrganismsPresent175.250.82133.5640.08 Absent28 TraumaPresent233.270.47922.3070.227 Absent22 Epithelial defect <36 sq mm3319.7092.564151.4950.004 >=36 sq mm 12

11. Illustrative Examples Group I Group II Group III At PresentationFinal Outcome

12. Patients receiving oral and topical voriconazole had earlier resolution of hypopyon (10 days) than patients receiving conventional antifungal treatment (12-16 days) (However, p>0.05.). Oral voriconazole and topical natamycin reigmen had best treatment success (73.3%). The risk factors for treatment failure in severe keratomycosis were age > 45 years and epithelial defect > 36 mm 2. All eyes with treatment failure had hypopyon at presentation. Voriconazole found to be equally efficacious and safe as conventional antifungal therapy in the treatment of severe keratomycosis. Aspergillus ulcers, typically resistant to conventional antifungal treatment, showed a much better therapeutic response to voriconazole. CONCLUSIONS